William Church, Trinity College – Cell Death and Parkinson’s Disease

On Trinity College Week: To help fight Parkinson’s disease, catch it earlier.

William Church, associate professor of chemistry and neuroscience, examines the importance of early detection.

Professor Church grew up in Virginia and received a B.S. in Chemistry at James Madison University.  After taking a year off to work in a hospital where he realized that studying the chemical causes of psychoactive drug side effects would be much more interesting than studying medicine, he obtained his Ph.D. in Analytical Chemistry at Emory University in Atlanta GA.  It was here that he was able to form a happy marriage between his two favorite science interests: analytical instrumentation and neuroscience.  Having never been west of the Mississippi, he accepted a postdoctoral appointment at the Salk Institute in La Jolla, Calif. working in the Clayton Foundation Peptide Biology Lab for Wiley Vale.  He initially came to Trinity in 1988 as a Visiting Professor in the Chemistry Department and was fortunate to be able to return to Trinity in 1995 in a joint appointment in the Chemistry Department and the Neuroscience Program.  He serves on the Health Professions Advising Committee, the IACUC, and is the faculty liaison for both the Women’s Soccer team and the Softball team.

Cell Death and Parkinson’s Disease

Humans suffering from Parkinson’s disease cannot be diagnosed until physical symptoms become observable.  Unfortunately, by the time a patient presents with the symptoms, over 75% of the brain cells responsible for motor control have been killed.  As a result, PD patients have less than 25% of their original dopamine brain cells in the substantia nigra when therapies are begun – this is a recipe for failure. 

If the cell death can be detected earlier (before physical symptoms appear) then behavioral and pharmacological therapies may be more effective in slowing the progression of the disease.  Our research is focused on detecting biomarkers in the blood which would indicate that this cell death is taking place abnormally, suggesting the presence of Parkinson’s Disease.  

The chemicals responsible for killing these brain cells are known as reactive oxygen species, or ROSs.  All cells produce ROSs, but in PD they are being produced at a higher rate than normal.  Cells also contain other chemicals, anti-oxidants, that act as sponges to ‘soak up’ these ROSs to prevent them from doing any damage.  We are using a very sophisticated instrument to measure the chemicals that are produced when a specific anti-oxidant, uric acid, neutralizes these ROSs by forming various uric acid metabolites.  If these metabolites are present in the blood at higher levels than normal, it would suggest that ROSs are being produced at a higher rate than normal and the patient may be at risk for developing Parkinsons’ Disease.  At this point, behavioral (exercise, diet) and/or pharmacological therapies could be initiated in an attempt to slow the disease progression. We are currently analyzing blood samples from genetically-engineered animal models of Parkinson’s Disease and correlating the amount of these uric acid metabolites with the amount of dopamine cell loss in the brains of these animals.